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Probing multiple proprietary pharmaceutical libraries in parallel via virtual screening allowed rapid expansion of the structure-activity relationship (SAR) around hit compounds with moderate efficacy against

An innovative pre-competitive virtual screening collaboration was engaged to validate and subsequently explore an imidazo[1,2-a]pyridine screening hit for visceral leishmaniasis. In silico probing of five proprietary pharmaceutical company libraries enabled rapid expansion of the hit chemotype, alleviating initial concerns about the core chemical structure while simultaneously improving antiparasitic activity and selectivity index relative to the background cell line. Subsequent hit optimization informed by the structure–activity relationship enabled by this virtual screening allowed thorough investigation of the pharmacophore, opening avenues for further improvement and optimization of the chemical series.

Two new γ-lactones, 3-epi-Waol A (1), and Waol C (2) were isolated, together with three known compounds [1-hydroxy-6-methyl-8-hydroxymethylxanthone, pestacin, and isopestacin], from the solid culture of the endophytic fungus Libertella blepharis that had been isolated from the mature leaf of Olyra latifolia, collected in the province of Colon, Republic of Panama. Elucidation of their structure was accomplished using 1D and 2D NMR spectroscopy in combination with IR spectroscopic and MS data. 3-epi-Waol A (1) showed a growth inhibition with IC50 values of 22.71 μM against the parasite Trypanosoma cruzi; and 22.46, 6.20, and 1.0 μM against MCF-7, HCT116, and H460 cancer cell lines, respectively.

Orexin (hypocretin) neuropeptides have, among others, been implicated in arousal/sleep control, and antagonizing the orexin signaling pathway has been previously demonstrated to promote sleep in animals and humans. This mechanism opens up a new therapeutic approach to curb excessive wakefulness in insomnia disorder rather than to promote sleep-related signaling. Here we describe the preclinical pharmacological in vitro and in silico characterization of lemborexant ((1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide)), a dual orexin receptor antagonist (DORA), as a novel experimental therapeutic agent for the symptomatic treatment of insomnia disorder and compare its properties to two other DORAs, almorexant and suvorexant. Lemborexant binds to both orexin receptors and functionally inhibits them in a competitive manner with low nanomolar potency, without any species difference apparent among human, rat, and mouse receptors. Binding and dissociation kinetics on both orexin receptors are rapid. Lemborexant is selective for both orexin receptors over 88 other receptors, transporters, and ion channels of important physiologic function. In silico modeling of lemborexant into the orexin receptors showed that it assumes the same type of conformation within the receptor-binding pocket as suvorexant, the π-stacked horseshoe-like conformation.

3-epi-Waol A (I) exhibits growth inhibition against the parasite Trypanosoma cruzi (IC50=22.71 μM), and against MCF-7 (IC50=22.46 μM), HCT116 (IC50=6.2 μM), and H460 (IC50=1.0 μM) cancer cell lines.

Anthraquinone is an important dye intermediate and is known also as a digest-aid chemical in pulp manufacturing since 20 years ago.Recent studies revealed, furthermore, that anthraquinone inhibited sulfate respiration of sulfate-reducing bacteria in the sludge of wastewater so that evolution of hydrogen sulfide was effectively diminished. Follow up fieldworks are under way.Here are presented two field-test results, one obtained at a force main line of the Wastewater Treatment Plant for the City of Tampa, Florida, and another obtained at an underground reservoir or a pit of a building in the city of Tokyo.The anthraquinone formulation is expected to make an excellent means of diminishing foul sulfurous odor and preventing sulfuric corrosion at public sewage systems, pulp and paper mills, fermentation and food-processing plants, dyehouses and oil fields.

The analysis of seven aliphatic carboxylic acids (formic, acetic, propionic, iso-butyric, n-butyric, iso-valeric and n-valeric acid) in anaerobic digestion process waters for biogas production was examined by ion-exclusion chromatography with dilute acidic eluents (benzoic acid, perfluorobutyric acid (PFBA) and sulfuric acid) and non-suppressed conductivity/ultraviolet (UV) detection. The columns used were a styrene/divinylbenzene-based strongly acidic cation-exchange resin column (TSKgel SCX) and a polymethacrylate-based weakly acidic cation-exchange resin column (TSKgel Super IC-A/C). Good separation was performed on the TSKgel SCX in shorter retention times. For the TSKgel Super IC-A/C, peak shape of the acids was sharp and symmetrical in spite of longer retention times. In addition, the mutual separation of the acids was good except for iso- and n-butyric acids. The better separation and good detection was achieved by using the two columns (TSKgel SCX and TSKgel Super IC-A/C connected in series), lower concentrations of PFBA and sulfuric acid as eluents, non-suppressed conductivity detection and UV detection at 210 nm. This analysis was applied to anaerobic digestion process waters. The chromatograms with conductivity detection were relatively simpler compared with those of UV detection. The use of two columns with different selectivities for the aliphatic carboxylic acids and the two detection modes was effective for the determination and identification of the analytes in anaerobic digestion process waters containing complex matrices.